Randomised clinical trials became an essential part of clinical research in the 1940s. They have led to many important innovations in treatment in all areas of medicine, not least in oncology. Those of us involved in clinical research are aware, however, that the ways we are constrained to publish our results can create a misleading impression. The standard structure of a clinical scientific article-introduction, patients and methods, results, discussion-and the way it is written can all too often give the impression that clinical research is more inductive than innovative. This constraint can conceal the exploratory nature of hypotheses that are being tested and our genuine uncertainty about the likely outcomes of a randomised trial at the time it is planned. It also obscures the sense of discovery that can prevail as we conduct the trial and analyse the results. I therefore make my case against this motion on the basis of the way clinical research happens in practice, using a number of examples from our own and others' research. These examples come mainly, but not exclusively, from the field of oncology.
Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. In the 1970s, however, there was genuine uncertainty and disagreement within the medical community about whether chemotherapy had a role in the treatment of SCLC. The drug combinations then in use were considered highly toxic, and toxicity was not as well controlled as it is today. Some clinicians were convinced that those using chemotherapy could be killing as many patients as they were helping and were probably curing none. The view was also expressed at the time that even if a minor survival benefit could be demonstrated, it would not justify the toxicity. In contrast, other clinicians were enthusiastic advocates of chemotherapy in the light of their own experiences.
We therefore conducted a multicentre randomised trial comparing multidrug chemotherapy versus selective palliative treatment, in which supportive care, radiotherapy, and minimal single-drug chemotherapy could be given as and when required to control symptoms. We made the comparison in terms of survival, adverse reactions, and quality of life, recognising the importance of all these endpoints [1]. The trial showed that with immediate multidrug chemotherapy, there was a large survival benefit (a doubling of median survival), better control of metastases, acceptable toxicity, and better quality of life in terms